A previously undetected pseudogene in the human alpha globin gene cluster

Abstract

The sequence of the DNA between two pseudogenes in the human α-like globin gene cluster has been determined. Comparison of this sequence with sequences from other α-like globin gene clusters revealed another pseudogene, ψα2, between the previously recognized pseudogenes ζ1 and ψα1. Therefore, the human α-like globin gene family is organized 5′-ζ2-ζ l-ψα2-ψαl-α2-αl-3′. The new pseudogene ψα2 is very close to ζ1, beginning only 65 base pairs 3′ to the polyadenylation site of ζ1. The first exon and the first intron of ψα2 are interrupted by large inserts which are flanked by short (6 to 8 base pairs) direct repeats. The pseudogene ψα2 lacks a promoter for transcription by RNA polymerase II, the first exon is highly divergent, one splice site is mutated, and five different frameshift mutations have occurred in the coding regions. Thus ψα2 cannot encode a globin polypeptide. This pseudogene was not recognized in previous hybridization analyses of the human α-like globin gene cluster, and our discovery of it by sequence analysis suggests that divergent copies of many genes may be present in the human genome. These divergent copies of a large number of genes may comprise a substantial fraction of the slowly renaturing DNA of mammalian genomes.